Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators.

BACKGROUND: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. METHODS: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. RESULTS: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. CONCLUSION: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.

[Quality indicators for rescue operations in terrorist attacks or other threats : A pilot study after the Würzburg terrorist attack of July 2016]. / Qualitätsindikatoren für rettungsdienstliche Einsätze bei Terroranschlägen oder anderen Bedrohungslagen : Eine Pilotstudie nach dem Würzburger Terroranschlag vom Juli 2016.

BACKGROUND: Terrorist attacks have become reality in Germany. The aim of this work was, after the Würzburg terrorist attack, to define quality indicators and application characteristics for rescue missions in life-threatening situations. The results can be used to record data from future missions using this template in order to make them comparable with each other. METHODS: After approval of the local ethic committee, the first step was to designate a group of experts in order to define the template in a consensus process. The next step was to perform the consensus process by defining the template. An independent expert for emergency medicine and disaster management reviewed and approved the results afterwards. RESULTS: The expert group defined 13 categories and 158 parameters that will further serve the systematic evaluation of the rescue mission of the Würzburg terror attack. Preliminary results of this evaluation process are given in this paper; the full evaluation has not yet been completed. DISCUSSION: In this study we first describe quality indicators and parameters suitable for the German rescue system in order to evaluate rescue operations for violence caused mass casualties. There is similar international documentation, but it does not specifically focus on life-threatening operations and are not adapted to the German context. CONCLUSION: There is an important need to systematically evaluate rescue missions after mass killing incidents. In this study we report a template of parameters and quality indicators in order to systematically evaluate mass violence events. The presented template is the result of an expert consensus process and may serve as a basis for further development and research.

Intrinsic AHR in IL-5 transgenic mice is dependent on CD4(+) cells and CD49d-mediated signaling.

Overexpression of interleukin (IL)-5 by the airway epithelium in mice using the rat CC10 promoter (NJ.1726 line) leads to several histopathologies characteristic of human asthma, including airway hyperreactivity (AHR). We investigated the contribution of B and T cells, as well as CD4 expression, to the development of AHR in IL-5 transgenic mice. NJ.1726 mice on a T cell or CD4 knockout background, but not on a B cell knockout background, lost intrinsic AHR. These effects occurred without decreases in IL-5 or eosinophils. We further investigated the contribution of alpha(4)-integrin signaling to the development of AHR in IL-5 transgenic mice through the administration of anti-CD49d (alpha(4)-integrin) antibody (PS/2). Administration of PS/2 resulted in immediate (16-h) inhibition of AHR. The inhibition of AHR was not associated with a decrease in airway eosinophils. These studies demonstrate that, despite the presence of increased levels of IL-5 and eosinophils in the lungs of NJ.1726 mice, CD4(+) cells and alpha(4)-integrin signaling are necessary for the intrinsic AHR that develops in IL-5 transgenic mice.

Membrane vesiculation function and exocytosis of wild-type and mutant matrix proteins of vesicular stomatitis virus.

Transfection of mammalian CV1 cells with a recombinant M-gene pTM1 plasmid, driven by vaccinia virus-expressed phage T7 polymerase, resulted in the expression of matrix (M) protein, which is progressively released from the exterior surface of the transfected-cell plasma membrane. Exocytosis of M protein begins 2 to 4 h posttransfection and reaches a peak by 10 to 16 h posttransfection; dye uptake studies reveal that > 97% of cells are alive and have intact membranes at 16 h posttransfection. Density gradient centrifugation and labeling with radioactive palmitic acid revealed that the M protein is released from cells in association with lipid vesicles. Expression of M-gene deletion mutants suggests that exocytosis of M protein requires the presence of a membrane-binding site at N-terminal amino acids 1 to 50. Cells transfected with the pTM1 plasmid containing the M gene of the temperature-sensitive mutant tsO23 expressed ample quantities of the mutant M protein at permissive (31 degrees C) and restrictive (39 degrees C) temperatures, but the exocytosis of the mutant M protein occurred only at the permissive temperature. The tsO23 M gene has three site-specific mutations resulting in amino acid substitutions at residues 21, 111, and 227. Expression of wild-type and mutant M genes with mutations or revertants at each of these sites resulted in exocytosis of M protein at the nonpermissive temperature only when wild-type leucine was present at residue 111, but M-protein exocytosis was restricted (to some extent even at the permissive temperature) when mutant phenylalanine was present at residue 111. Past and present data indicate that a specific structural conformation of the M protein is responsible for the formation and budding of vesicles, a property of the M protein which probably also promotes vesicular stomatitis virus assembly and budding of virions from host cells.

Membrane-binding domains and cytopathogenesis of the matrix protein of vesicular stomatitis virus.

The membrane-binding affinity of the matrix (M) protein of vesicular stomatitis virus (VSV) was examined by comparing the cellular distribution of wild-type (wt) virus M protein with that of temperature-sensitive (ts) and deletion mutants probed by indirect fluorescent-antibody staining and fractionation of infected or plasmid-transfected CV1 cells. The M-gene mutant tsO23 caused cytopathic rounding of cells infected at permissive temperature but not of cells at the nonpermissive temperature; wt VSV also causes rounding, which prohibits study of M protein distribution by fluorescent-antibody staining. Little or no M protein can be detected in the plasma membrane of cells infected with tsO23 at the nonpermissive temperature, whereas approximately 20% of the M protein colocalized with the membrane fraction of cells infected with tsO23 at the permissive temperature. Cells transfected with a plasmid expressing intact 229-amino-acid wt M protein (M1-229) exhibited cytopathic cell rounding and actin filament dissolution, whereas cells retained normal polygonal morphology and actin filaments when transfected with plasmids expressing M proteins truncated to the first 74 N-terminal amino acids (M1-74) or deleted of the first 50 amino acids (M51-229) or amino acids 1 to 50 and 75 to 106 (M51-74/107-229). Truncated proteins M1-74 and M51-229 were readily detectable in the plasma membrane and cytosol of transfected cells as determined by both fluorescent-antibody staining and cell fractionation, as was the plasmid-expressed intact wt M protein. However, the expressed doubly deleted protein M51-74/107-229 could not be detected in plasma membrane by fluorescent-antibody staining or by cell fractionation, suggesting the presence of two membrane-binding sites spanning the region of amino acids 1 to 50 and amino acids 75 to 106 of the VSV M protein. These in vivo data were confirmed by an in vitro binding assay in which intact M protein and its deletion mutants were reconstituted in high- or low-ionic-strength buffers with synthetic membranes in the form of sonicated unilammelar vesicles. The results of these experiments appear to confirm the presence of two membrane-binding sites on the VSV M protein, one binding peripherally by electrostatic forces at the highly charged NH2 terminus and the other stably binding membrane integration of hydrophobic amino acids and located by a hydropathy plot between amino acids 88 and 119.

Beta 2-microglobulin clearance in neonates: index of tubular maturation.

Serum and urinary beta 2-microglobulin (beta 2M) were studied by enzyme immunoassay in 28 normal neonates at day 1 and day 4 of life in relation to gestational age (GA) and postnatal age (PNA). The infants were grouped according to GA; 10 with GA ranging from 32 to 35 weeks (mean 33.5 weeks) and 18 with GA ranging from 36 to 41 weeks (mean 38.3 weeks). Serum beta 2M varied directly with both GA and PNA. When values for serum beta 2M were related to conceptional age (CA), a significant positive correlation was present for all the infants studied (r = 0.68, P less than 0.01). Fractional excretion of beta 2M (FE beta 2M) decreased as a function of both GA and PNA. When a comparison of FE beta 2M was made in infants of all CA, a significant inverse correlation was noted for infants with CA less than or equal to 35 weeks (r = -0.89, P less than 0.001). The fall in FE beta 2M reached a plateau by 36 weeks. The highest FE beta 2M (33%) was observed in infants of 32 weeks CA who had the lowest filtered beta 2M (F beta 2M). No statistically significant relationship between changes in FE beta 2M and fractional urine flow rate was observed within each of the CA categories (infants less than or equal to 35 weeks, r = 0.21, P = 0.28; infants greater than or equal to 36 weeks, r = 0.25, P = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Superoxide dismutase and glutathione peroxidase abnormalities in erythrocytes and lymphoid cells in Down syndrome.

After validating a superoxide dismutase (SOD) assay, this enzyme was measured together with a large series of cell age sensitive marker enzymes, in the erythrocytes of 24 persons with the 24 persons without Down syndrome. In addition to the expected elevation of SOD-1, significant elevations of erythrocyte glutathione peroxidase (GSHPxase) and phosphofructokinase activities were found in Down syndrome. None of these changes could be accounted for by a decreased mean red cell age. The elevation of GSHPxase was also found in lymphoid cells but does not represent a gene dose effect at this locus. Rather, the elevation of GSHPxase in Down syndrome may represent an adaptive metabolic response to the increased hydrogen peroxide produced by the triplicated SOD-1 gene dose in trisomy 21. Since tissue GSHPxase activity can be manipulated via the enzyme's obligatory selenium co-factor, our data suggest the need to establish blood and tissue levels of selenium in Down syndrome and to correlate selenium, GSHPxase and phenotypic dysfunction in this disorder.

Detection of homozygotes and heterozygotes with methylenetetrahydrofolate reductase deficiency.

Specific enzyme assay is required for the diagnosis of homocystinuria due to methylenetetrahydrofolate reductase deficiency. A rapid and accurate method has been developed using "pure" peripheral lymphocyte preparations. Triplicate determinations showed highly reproducible results. With the use of the mean of triplicate determinations in the presence of flavinadenine dinucleotide, there was complete segregation among the homozygotes, heterozygotes, and normal subjects. This method provides a rapid diagnosis in affected subjects and a simple means for the determination of heterozygotes for genetic counseling.

Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions.

A 5-year-old boy was found to have severe rickets in association with hyperpigmented, linear, verrucous, epidermal tumors, typical of the epidermal nevus syndrome. Normocalcemia (9.6 mg/dl), hypophosphatemia (2.0 mg/dl), elevated serum alkaline phosphatase concentration (313 IU), decreased renal tubular reabsorption of phosphorus (35%), radiologic evidence of rickets, and lack of response to usual therapeutic doses of vitamin D suggested hypophosphatemic vitamin D-resistant rickets. Therapy with vitamin D in doses to 750,000 IU and oral phosphate, 2.0 gm/day, failed to induce healing of the rickets. A subtotal parathyroidectomy performed when the patient was 9 years old was also without effect. When he was 12 years old several fibroangiomas on the face and left lower limb were excised. Within three months all biochemical abnormalities resolved and radiologic evidence of healing was observed. A portion of excised tissue was homogenized and injection of the supernate into a 6-week-old puppy induced excessive phosphaturia. The data suggest that the rickets was induced by a phosphaturic substance extractable from the tumors.

Folic acid nonresponsive homocystinuria due to methylenetetrahydrofolate reductase deficiency.

Four siblings from a family with 11 children of Irish ancestry were observed to suffer from an essentially identical clinical illness, consisting of delayed psychomotor development in infancy and childhood, severe mental retardation, and upper motor neuron dysfunction. Death occurred at an early age in three siblings. In cases in which detailed physical examinations were performed, ectopia lentis, marfanoid features, and severe bony deformities were absent. Homocystinuria, homocystinemia, relatively normal concentrations of methionine and cystine in tissue fluids, and absence of methylmalonic aciduria were found. A deficiency of methylenetetrahydrofolate reductase was demonstrated in cultured skin fibroblasts from two siblings. Postmortem examination of two of the three patients who died showed extensive vascular thrombosis. No biochemical improvement was observed in the surviving child following treatment with large doses of folic acid.

A defect in tryptophan metabolism.

Oral tryptophan loading tests were performed in a patient with photosensitive pellagra-like skin rash and cerebellar ataxia but without hyperaminoaciduria. Plasma tryptophan concentrations after loading were similar in the patient and control subjects. Average urinary excretion of tryptophan in the patient from 0 to 6 and 6 to 12 hr was 2.69 and 2.58 mumol/kg, respectively; that in the control subjects was 0.82 and 0.34 mumol/kg, respectively. However, the average renal clearance of tryptophan during the first 6 hr of the loading tests in the patient was 0.757 ml plasma/1.73 m2 and that in the control subjects was 0.706 ml plasma/1.73 m2. Renal excretion of kynurenine in the patient was markedly decreased. The average from 0 to 6 and 6 to 12 hr in the patient was 1.90 and 1.13 mumol/kg, respectively; that in the control subjects was 12.90 and 18.15 mumol/kg, respectively. Under ultraviolet light, paper chromatograms of urine from the patient showed a deficiency of xanthurenic acid, kynurenic acid, kynurenine, and formylkynurenine. The deficiency of formylkynurenine in the patient's urine was confirmed by staining the paper chromatograms with Ehrlich's reagent. The patient was "sensitive" to oral nicotinic acid treatment; however, oral nicotinamide was well tolerated with improvement in the photosensitive skin rash.

Biochemical, morphological and hybrid studies in hyperprolinemic mice.

Hyperprolinemia, hyperprolinuria and hydroxyprolinuria were observed in PRO/Re mice. Hepatic proline oxidase activity in PRO/Re mice was markedly deficient. It was demonstrated that the deficiency of proline oxidase activity was not due to the presence of an inhibitor. The mutant enzyme in PRO/Re showed no difference in heat stability but had a poor affinity for the substrate, L-proline as compared to normal enzymes. There was no significant proteinuria or hematuria in PRO/Re mice. Their serum protein and blood urea nitrogen were normal. Morphologic studies by light and electron microscopy demonstrated no abnormality in the renal tissues of PRO/Re up to 6 months of age, suggesting that hyperprolinemia did not cause renal damage. Pedigree studies showed that F1 generation (PRO/Re x CD 1) had approximately 50 percent of normal proline oxidase activity and significantly higher plasma proline. The distribution of hepatic proline oxidase activity in F2 GENERATION (F1 x F1) was characteristic of an autosomal recessive trait.